The Impact of Geography in Hepatocellular Carcinoma: A Retrospective Population Based Study

Background: The treatment of hepatocellular carcinoma (HCC) includes different therapeutic modalities and multidisciplinary tumor board reviews. The impact of geography and treatment center type (quaternary vs. non-quaternary) on access to care is unclear. Methods: A retrospective chart review was performed on HCC patients who received sorafenib in British Columbia from 2008 to 2016. Patients were grouped by Statistics Canada population center (PC) size criteria: large PC (LPC), medium PC (MPC), and small PC (SPC). Access to specialists, receipt of liver-directed therapies, and survival outcomes were compared between the groups. Results: Of 286 patients, the geographical distribution was: LPC: 75%; MPC: 16%; and SPC: 9%. A higher proportion of Asians (51% vs. 9% vs. 4%; p < 0.001), Child–Pugh A (94% vs. 83% vs. 80%; p = 0.022), and hepatitis B (37% vs. 15% vs. 4%; p < 0.001) was observed in LPC vs. MPC vs. SPC, respectively. LPC patients were more likely referred to a hepatologist (62% vs. 48% vs. 40%; p = 0.031) and undergo transarterial chemoembolization (TACE) (43% vs. 24% vs. 24%; p = 0.018). Sixty percent were treated at a quaternary center, and the median overall survival (OS) was higher for patients treated at a quaternary vs. non-quaternary center (28.0 vs. 14.6 months, respectively; p < 0.001) but similar when compared by PC size. Treatment at a quaternary center predicted an improved survival on multivariate analysis (hazard ratio (HR): 0.652; 95% confidence interval (CI): 0.503–0.844; p = 0.001). Conclusions: Geography did not appear to impact OS but patients from LPC were more likely to be referred to hepatology and undergo TACE. Treatment at a quaternary center was associated with an improved survival.

Doyle-Kirmse Reaction Using 3,3-Difluoroallyl Sulfide and N-Sulfonyl-1,2,3-triazole: An Efficient Access to gem-Difluoroallylated Multifunctional Quaternary Carbon

Doyle-Kirmse reaction of N-sulfonyl-1,2,3-triazole with 3,3-difluoroallyl sulfide through Rh(II)-catalyzed [2,3]-sigmatropic rearrangement has been developed, which affords an efficient access to multifunctional quaternary center containing aryl, imino, thio, and brominated gem-difluoroallyl....

Concise synthesis of α-cyano tetrahydroisoquinolines with a quaternary center via Strecker reaction

Concise synthesis of α-cyano tetrahydroisoquinolines with a quaternary center was successfully realized, furnishing products with up to 99% yield and an isomerization was observed under alkaline conditions, giving the isomer via [1,3]-H shift.

All-carbon [3 + 2] cycloaddition in natural product synthesis

Many natural products possess interesting medicinal properties that arise from their intriguing chemical structures. The highly-substituted carbocycle is one of the most common structural features in many structurally complicated natural products. However, the construction of highly-substituted, stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all-carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020 (inclusive).

Geographical Distance from Quaternary Treatment Center Does Not Impact Choice of Upfront Therapy, Clinical Trial Participation and Outcomes in Patients with Newly Diagnosed AML

Upfront therapy for newly diagnosed patients with acute myeloid leukemia (AML) includes intensive induction chemotherapy with curative intent, low dose chemotherapy, best supportive care, and clinical trials. The choice between these therapies is influenced by multiple factors including age, cytogenetic and molecular mutations, and performance status. In our single payer provincial health care system, induction chemotherapy and clinical trials are only offered at a small number of specialized quaternary care centers with geographically large catchment areas. As a result, some patients are required to travel long distances for their appointments, which may constitute a barrier to care, especially among elderly patients. We therefore asked whether distance from the quaternary center influences the choice of care for AML. We reviewed the records of patients ≥18 years of age diagnosed with AML from 2015-2017 and assessed at our quaternary care center in Toronto, Canada. We compared upfront therapy choice and survival between patients living close versus distant from the cancer center (empirically defined as &lt;50 km versus &gt;50km) and stratified by age. A total of 675 patients were assessed by our quaternary center for a new diagnosis of AML during the timeframe studied. Of those patients, 477 (71%) patients lived ≤50km, and 198 (29%) patients lived &gt;50km from the quaternary center. The overall median distance from patient residence to the quaternary center was 33.2km (range: 1-1791km), and the median distance of patients in the &gt;50km group was 93km (range: 50.2-1791km). Age, sex, baseline Eastern Cooperative Oncology Group Performance Status (ECOG), and cytogenetic risk were not significantly different between the two groups. There were no differences in the proportion of patients receiving induction chemotherapy or clinical trial as upfront therapy between patients living close versus distant from the quaternary center, even when stratified for age ≥70 years. There was no difference in overall survival between patients living ≤50km versus &gt;50km from the quaternary center either overall, or when stratified by age. In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, access to clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single payer environment. Disclosures Gupta: Bristol MyersSquibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Research Funding; Pfizer: Consultancy; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees. Maze:Novartis: Honoraria; Pfizer: Consultancy; Takeda: Research Funding. McNamara:Novartis: Honoraria. Schimmer:Takeda: Honoraria, Research Funding; Novartis: Honoraria; Jazz: Honoraria; Otsuka: Honoraria; Medivir AB: Research Funding; AbbVie Pharmaceuticals: Other: owns stock .